2024
Yeast 26S proteasome nuclear import is coupled to nucleus-specific degradation of the karyopherin adaptor protein Sts1
Breckel C, Johnson Z, Hickey C, Hochstrasser M. Yeast 26S proteasome nuclear import is coupled to nucleus-specific degradation of the karyopherin adaptor protein Sts1. Scientific Reports 2024, 14: 2048. PMID: 38267508, PMCID: PMC10808114, DOI: 10.1038/s41598-024-52352-5.Peer-Reviewed Original ResearchConceptsProteasome storage granulesNuclear importUbiquitin-independent proteasomal degradationProteasome degradation in vitroYeast Saccharomyces cerevisiaeProlonged glucose starvationNuclear import factorsUbiquitin-proteasome systemProteasome interactionGlucose starvationKaryopherin proteinsProteasomal degradationNuclear transportCellular homeostasisDegradation in vivoSTS1KaryopherinProtein degradationProteasomeDegradation in vitroGlucose refeedingStorage granulesProteinEukaryotesRanGTP
2023
Sis2 regulates yeast replicative lifespan in a dose-dependent manner
Ölmez T, Moreno D, Liu P, Johnson Z, McGinnis M, Tu B, Hochstrasser M, Acar M. Sis2 regulates yeast replicative lifespan in a dose-dependent manner. Nature Communications 2023, 14: 7719. PMID: 38012152, PMCID: PMC10682402, DOI: 10.1038/s41467-023-43233-y.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell Cycle ProteinsDNA ReplicationLongevitySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsYeast replicative lifespanReplicative lifespanRNA-seq experimentsCoenzyme A biosynthesis pathwayYeast lifespanYeast strainsStrain librariesLifespan regulationRNA-seqGene networksDose-dependent mannerLifespan extensionTranscriptional increaseYeastLifespan measurementsWild-typeGenesMachinery componentsStrainMicrofluidic platformApplications of microfluidic platformsLifespanDeletionCoenzymePathwaySpecies-specific protein–protein interactions govern the humanization of the 20S proteasome in yeast
Sultana S, Abdullah M, Li J, Hochstrasser M, Kachroo A. Species-specific protein–protein interactions govern the humanization of the 20S proteasome in yeast. Genetics 2023, 225: iyad117. PMID: 37364278, PMCID: PMC10471208, DOI: 10.1093/genetics/iyad117.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsYeast proteasomeLocal protein-protein interactionsSpecific protein-protein interactionsYeast proteasome subunitsVast evolutionary distancesC-terminal tailFull-length tailThousands of genesHigh-throughput pipelineYeast counterpartEvolutionary divergenceEvolutionary distanceAssembly intermediatesHuman genesProteasome subunitsComplementationProteasomeSubunitsYeastGenesDistinct interactionsCore assemblyHuman β3Β3 subunitProteasomes: Isolation and Activity Assays
Li Y, Tomko R, Hochstrasser M. Proteasomes: Isolation and Activity Assays. Current Protocols 2023, 3: e717. PMID: 37026813, PMCID: PMC10337785, DOI: 10.1002/cpz1.717.Peer-Reviewed Original ResearchConceptsRegulatory particleOne-step purification schemeCore particlesMultisubunit protease complexUbiquitin-proteasome systemUbiquitin polypeptidesUnneeded proteinsYeast SaccharomycesProtein substratesProtease complexProteasomeGel filtration stepPurification schemeProteolytic activityEukaryotesSaccharomycesPolypeptideProteinSubstrateAssaysComplexesEctopic RING activity at the ER membrane differentially impacts ERAD protein quality control pathways
Mehrtash A, Hochstrasser M. Ectopic RING activity at the ER membrane differentially impacts ERAD protein quality control pathways. Journal Of Biological Chemistry 2023, 299: 102927. PMID: 36682496, PMCID: PMC9950527, DOI: 10.1016/j.jbc.2023.102927.Peer-Reviewed Original ResearchMeSH KeywordsEndoplasmic Reticulum-Associated DegradationGene ExpressionSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitin-Protein LigasesUbiquitinationConceptsEndoplasmic reticulum-associated degradationProtein quality control pathwaysQuality control pathwaysER membraneE3 complexControl pathwaysRING-type E3 ubiquitin ligasesE3 ubiquitin ligasesDominant negative mutantDoa10 substratesMisfolded proteinsUbiquitin ligasesERAD factorsMammalian cellsRING domainUBC6Substrate turnoverLuminal substratesDoa10OverexpressionPathway defectsYeastPathwayRing activityMembrane
2001
SP-RING for SUMO New Functions Bloom for a Ubiquitin-like Protein
Hochstrasser M. SP-RING for SUMO New Functions Bloom for a Ubiquitin-like Protein. Cell 2001, 107: 5-8. PMID: 11595179, DOI: 10.1016/s0092-8674(01)00519-0.Peer-Reviewed Original Research
2000
The Doa4 Deubiquitinating Enzyme Is Functionally Linked to the Vacuolar Protein-sorting and Endocytic Pathways
Amerik A, Nowak J, Swaminathan S, Hochstrasser M. The Doa4 Deubiquitinating Enzyme Is Functionally Linked to the Vacuolar Protein-sorting and Endocytic Pathways. Molecular Biology Of The Cell 2000, 11: 3365-3380. PMID: 11029042, PMCID: PMC14998, DOI: 10.1091/mbc.11.10.3365.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAmino Acid SequenceBreast NeoplasmsCysteine EndopeptidasesEndocytosisEndopeptidasesEndosomal Sorting Complexes Required for TransportFemaleFungal ProteinsGenotypeHumansMolecular Sequence DataMultienzyme ComplexesMutagenesisProteasome Endopeptidase ComplexRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSequence Homology, Amino AcidSubstrate SpecificitySuppression, GeneticUbiquitin ThiolesteraseUbiquitinsVacuolesConceptsPrevacuolar compartmentDeubiquitinating enzymeVacuolar protein sorting (VPS) pathwayFluorescent proteinEndomembrane protein traffickingProtein sorting pathwaysUbiquitinated membrane proteinsVacuolar protein sortingClass E compartmentSpontaneous extragenic suppressorsGreen fluorescent proteinExtragenic suppressorsProtein sortingProtein traffickingProtein deubiquitinationUbiquitin recyclingPathway substrateE compartmentMembrane proteinsEndocytic pathwayUbiquitinated intermediatesDifferent genesMultivesicular bodiesNuclear distributionUnanticipated connectionsEvolution and function of ubiquitin-like protein-conjugation systems
Hochstrasser M. Evolution and function of ubiquitin-like protein-conjugation systems. Nature Cell Biology 2000, 2: e153-e157. PMID: 10934491, DOI: 10.1038/35019643.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCoenzymesEvolution, MolecularHumansMolecular Sequence DataProteinsSaccharomyces cerevisiaeSequence AlignmentSignal TransductionUbiquitinsA viable ubiquitin‐activating enzyme mutant for evaluating ubiquitin system function in Saccharomyces cerevisiae
Swanson R, Hochstrasser M. A viable ubiquitin‐activating enzyme mutant for evaluating ubiquitin system function in Saccharomyces cerevisiae. FEBS Letters 2000, 477: 193-198. PMID: 10908719, DOI: 10.1016/s0014-5793(00)01802-0.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceDNA PrimersLigasesMutationSaccharomyces cerevisiaeUbiquitin-Activating EnzymesUbiquitin-Protein LigasesUbiquitinsConceptsUbiquitin system functionActivation of ubiquitinUbiquitin-activating enzymeProteasome-independent degradationUbiquitin systemCellular processesPathway substrateMammalian cellsHypomorphic alleleProtein modificationEnzyme mutantsMutant allelesMembrane receptorsMutantsUbiquitinComparable mutantsSaccharomycesCell functionAllelesProteasomeYeastProteinEnzymeDegradationE1The Yeast ULP2 (SMT4) Gene Encodes a Novel Protease Specific for the Ubiquitin-Like Smt3 Protein
Li S, Hochstrasser M. The Yeast ULP2 (SMT4) Gene Encodes a Novel Protease Specific for the Ubiquitin-Like Smt3 Protein. Molecular And Cellular Biology 2000, 20: 2367-2377. PMID: 10713161, PMCID: PMC85410, DOI: 10.1128/mcb.20.7.2367-2377.2000.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionChromosomesCysteine EndopeptidasesDNA DamageEndopeptidasesFungal ProteinsHydroxyureaMitosisMolecular Sequence DataMutationRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidSmall Ubiquitin-Related Modifier ProteinsSUMO-1 ProteinTemperatureUbiquitinsConceptsCell cycle checkpoint arrestTemperature-sensitive growthCentromere-binding proteinsUbiquitin-like proteinDNA-damaging agentsAbnormal cell morphologyYeast SMT3Number suppressorGene EncodesPleiotropic phenotypesChromosome stabilityMutant accumulatesSingle mutantsCheckpoint arrestUlp2SUMO-1Smt3Ulp1DNA damageMutantsReplication inhibitionProteinCell morphologyNormal kineticsCell function
1999
The Doa4 Deubiquitinating Enzyme Is Required for Ubiquitin Homeostasis in Yeast
Swaminathan S, Amerik A, Hochstrasser M. The Doa4 Deubiquitinating Enzyme Is Required for Ubiquitin Homeostasis in Yeast. Molecular Biology Of The Cell 1999, 10: 2583-2594. PMID: 10436014, PMCID: PMC25490, DOI: 10.1091/mbc.10.8.2583.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCytoskeletal ProteinsEndopeptidasesEndosomal Sorting Complexes Required for TransportFungal ProteinsHomeostasisMutationPeptide HydrolasesProteasome Endopeptidase ComplexSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitin ThiolesteraseUbiquitinsVacuolesVesicular Transport ProteinsConceptsDeubiquitinating enzymeAttachment of ubiquitinUbiquitin-dependent proteolysisYeast Saccharomyces cerevisiaeWild-type cellsCell surface proteinsAdditional ubiquitinVacuolar proteolysisUbiquitinated substratesUbiquitin homeostasisCellular proteinsMembrane proteinsUbiquitinated intermediatesSaccharomyces cerevisiaeGenetic dataDoa4Loss of viabilityUbiquitin depletionUbiquitinProteolytic intermediatesProteasomeSurface proteinsUbiquitin degradationEventual degradationProteinEukaryotic 20S proteasome catalytic subunit propeptides prevent active site inactivation by N‐terminal acetylation and promote particle assembly
Arendt C, Hochstrasser M. Eukaryotic 20S proteasome catalytic subunit propeptides prevent active site inactivation by N‐terminal acetylation and promote particle assembly. The EMBO Journal 1999, 18: 3575-3585. PMID: 10393174, PMCID: PMC1171436, DOI: 10.1093/emboj/18.13.3575.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAmino Acid SequenceArylamine N-AcetyltransferaseBinding SitesCatalysisCatalytic DomainCell DivisionCysteine EndopeptidasesEndopeptidasesFungal ProteinsIsoenzymesMolecular Sequence DataMultienzyme ComplexesPeptide FragmentsPhenotypeProteasome Endopeptidase ComplexSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence DeletionThreonineConceptsProteasome assemblyFirst biochemical evidenceN-terminal acetylationUbiquitin-proteasome systemProteolytic active sitesBarrel-shaped structureCatalytic threonine residueYeast 20S proteasomeThreonine residuesHeptameric ringsProteasome biogenesisEnvironmental stressNovel functionDistinct functionsLarge proteaseDifferent subunitsParticle assemblyAlpha-amino groupSpecific peptidase activityProteasomeCatalytic mechanismSite inactivationPeptidase activityCritical functionsSubunitsA new protease required for cell-cycle progression in yeast
Li S, Hochstrasser M. A new protease required for cell-cycle progression in yeast. Nature 1999, 398: 246-251. PMID: 10094048, DOI: 10.1038/18457.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell Cycle ProteinsCloning, MolecularCysteine EndopeptidasesEscherichia coliFungal ProteinsG2 PhaseHumansMitosisMolecular Sequence DataMutagenesisRecombinant Fusion ProteinsRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidSmall Ubiquitin-Related Modifier ProteinsSubstrate SpecificitySUMO-1 ProteinUbiquitinsConceptsSUMO-1Cell cycleUbl-specific proteasesUbiquitin-like proteinCell cycle progressionG2/M phaseProtein functionSmt3Cellular proteinsDeubiquitinating enzymeUlp1Distant similarityUbiquitinHuman pathogensM phaseProteinEssential roleNew proteaseProteaseViral proteaseProtein conjugationEukaryotesMutantsUBLYeast
1998
Degradation Signal Masking by Heterodimerization of MATα2 and MATa1 Blocks Their Mutual Destruction by the Ubiquitin-Proteasome Pathway
Johnson P, Swanson R, Rakhilina L, Hochstrasser M. Degradation Signal Masking by Heterodimerization of MATα2 and MATa1 Blocks Their Mutual Destruction by the Ubiquitin-Proteasome Pathway. Cell 1998, 94: 217-227. PMID: 9695950, DOI: 10.1016/s0092-8674(00)81421-x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCysteine EndopeptidasesDimerizationDiploidyFungal ProteinsHaploidyIntramolecular TransferasesLipoproteinsMating FactorMolecular Sequence DataMultienzyme ComplexesMutationPeptidesPheromonesProteasome Endopeptidase ComplexProtein Structure, SecondarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitinsConceptsUbiquitin-proteasome pathwayDegradation signalCoiled-coil interactionsAlpha haploid cellsRegulated turnoverMultiprotein complexesHaploid cellsPathway substrateTranscription factorsExtensive mutagenesisProteolytic signalMolecular mechanismsCell typesHeterodimerizationSuch regulationCritical determinantPathwayAlpha2MATa1MATα2Signal maskingRepressorHaploidsSaccharomycesMutagenesisUnified nomenclature for subunits of the Saccharomyces cerevisiae proteasome regulatory particle
Finley D, Tanaka K, Mann C, Feldmann H, Hochstrasser M, Vierstra R, Johnston S, Hampton R, Haber J, McCusker J, Silver P, Frontali L, Thorsness P, Varshavsky A, Byers B, Madura K, Reed S, Wolf D, Jentsch S, Sommer T, Baumeister W, Goldberg A, Fried V, Rubin D, Glickman M, Toh-e A. Unified nomenclature for subunits of the Saccharomyces cerevisiae proteasome regulatory particle. Trends In Biochemical Sciences 1998, 23: 244-245. PMID: 9697412, DOI: 10.1016/s0968-0004(98)01222-5.Peer-Reviewed Original ResearchMolecular Organization of the 20S Proteasome Gene Family from Arabidopsis thaliana
Fu H, Doelling J, Arendt C, Hochstrasser M, Vierstra R. Molecular Organization of the 20S Proteasome Gene Family from Arabidopsis thaliana. Genetics 1998, 149: 677-692. PMID: 9611183, PMCID: PMC1460176, DOI: 10.1093/genetics/149.2.677.Peer-Reviewed Original ResearchConceptsSubunit geneCross-species complementationCollection of cDNAsMolecular organizationAbnormal intracellular proteinsBeta-subunit geneProteasome gene familyProteasome alphaPlant ArabidopsisYeast orthologArabidopsis thalianaGenomic clonesGene familyYeast complexSingle geneUbiquitin conjugationProteolytic complexBeta polypeptideSubunit arrangementProteasome subunitsIntracellular proteinsProteasomeGenesSymmetric organizationArabidopsisAn Evolutionarily Conserved Gene on Human Chromosome 5q33–q34,UBH1,Encodes a Novel Deubiquitinating Enzyme
Hansen-Hagge T, Janssen J, Hameister H, Papa F, Zechner U, Seriu T, Jauch A, Becke D, Hochstrasser M, Bartram C. An Evolutionarily Conserved Gene on Human Chromosome 5q33–q34,UBH1,Encodes a Novel Deubiquitinating Enzyme. Genomics 1998, 49: 411-418. PMID: 9615226, DOI: 10.1006/geno.1998.5275.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCaenorhabditis elegansChromosome MappingChromosomes, Human, Pair 14Chromosomes, Human, Pair 5Conserved SequenceDNA PrimersEndopeptidasesEvolution, MolecularHumansIn Situ HybridizationLeukemiaMiceMolecular Sequence DataMultigene FamilyNervous SystemNeuronsPolymerase Chain ReactionPseudogenesSaccharomyces cerevisiaeSequence AlignmentSequence Homology, Amino AcidTranscription, GeneticTranslocation, GeneticUbiquitin ThiolesteraseConceptsGene familyDeubiquitinating enzymeNovel multigene familyGalactosidase fusion proteinSitu hybridizationNovel deubiquitinating enzymeNorthern blot analysisConserved geneCaenorhabditis elegansHypothetical proteinsMultigene familyHuman genesLow-level expressionFunctional membersHuman chromosomesProtein displayFusion proteinMouse tissuesEscherichia coliChromosome 5q33Blot analysisBreakpoint sequencesEnzyme 1GenesEnzymeThere’s the Rub: a novel ubiquitin-like modification linked to cell cycle regulation
Hochstrasser M. There’s the Rub: a novel ubiquitin-like modification linked to cell cycle regulation. Genes & Development 1998, 12: 901-907. PMID: 9531529, DOI: 10.1101/gad.12.7.901.Peer-Reviewed Original Research
1997
In vivo disassembly of free polyubiquitin chains by yeast Ubp14 modulates rates of protein degradation by the proteasome
Amerik A, Swaminathan S, Krantz B, Wilkinson K, Hochstrasser M. In vivo disassembly of free polyubiquitin chains by yeast Ubp14 modulates rates of protein degradation by the proteasome. The EMBO Journal 1997, 16: 4826-4838. PMID: 9305625, PMCID: PMC1170118, DOI: 10.1093/emboj/16.16.4826.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCarbon-Nitrogen LyasesEndopeptidasesFungal ProteinsGene Expression Regulation, FungalGenes, FungalHumansImmunoblottingLyasesMolecular Sequence DataMutagenesis, Site-DirectedPeptide HydrolasesPhenotypeProteasome Endopeptidase ComplexProtein BindingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSubstrate SpecificityUbiquitinsConceptsUnanchored ubiquitin chainsUbiquitin chainsProtein degradationFree ubiquitin chainsUbiquitin-dependent proteolysisWild-type cellsActive site mutantsFree polyubiquitin chainsEukaryotic proteinsFunctional homologComplementation analysisPolyubiquitin chainsSteady-state levelsDeubiquitinating enzymeUbp14Site mutantsIsopeptidase TCellular proteasesYeast cellsProteasomeInhibition of degradationStriking accumulationProteolysisProteinCellsIdentification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation
Arendt C, Hochstrasser M. Identification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 7156-7161. PMID: 9207060, PMCID: PMC23776, DOI: 10.1073/pnas.94.14.7156.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCysteine EndopeptidasesMultienzyme ComplexesProteasome Endopeptidase ComplexSaccharomyces cerevisiaeStructure-Activity RelationshipSubstrate SpecificityConceptsActive siteN-terminal threonineBeta subunitDistinct peptidase activitiesMost minor effectsSubunit ringDifferent beta subunitsCorresponding threonineActive site formationUbiquitin-dependent proteolysisDegradation of substratesProteasome active sitesYeast proteasomeArchaeal proteasomeDifferent eukaryotesActive-site nucleophileUbiquitin pathwayHeptameric ringsBasic residuesSubunit interactionsAcidic residuesAlpha subunitSubstrateProteasomePeptide substrates